The unifying theme of this program is the Biology of the Cutaneous Epithelium, a term inclusive of the epidermis and the follicular epithelium. This Program is composed of five projects, each headed by established investigators, and three cores. The five component projects focus on distinct, yet related aspects of skin biology, and all projects are designed to study fundamental cellular mechanisms controlling cell differentiation, maintenance of tissue structure, and response to injury. Furthermore, this Program includes investigators outside of Dermatology, thereby broadening the scientific foundation of skin-related research at Washington University. The Program begins with studies on skin development and cellular differentiation. Dr. Raphael Kopan (Project 1) will study the role of Notch and related cell-signaling molecules during stages of cell-fate determination and differentiation of the developing and the nature, cycling hair follicle. Dr. David Ornitz (Project 2) proposes to study the functional and biochemical interactions of fibroblast growth factor-10 (FGF-10), which is produced in the dermis, and its receptor on keratinocytes during development and in response to injury. The molecular determinants required for formation of desmosomes and their role in keratinocyte signaling and epidermal morphogenesis will be addressed by Dr. Sergey Troyanovsky (Project 3). For Project 4, Dr. William Parks will determine the precise and distinct cell-matrix interactions that regulate the activation, maintenance, and deactivation of keratinocytes in response to wounding and how these events control expression of wound-related genes. Dr. Michael Caparon (Project 5) focuses on how group A streptococcus interact with the epidermis and how keratinocytes respond to and defend against bacterial infection. Three Cores will support the effort of the Program investigators. The Administrative Core (Core A) will be responsible for Program management and coordination. The Transgenic Core (Core B) will create genetically- defined animals (e.g., knock-outs, conditional knock-outs, transgenics) for all Program investigators, and in situ hybridizations for all projects. Thus, this new Program is integrated around a common scientific theme and goal, thereby promoting many interactions, and is supported by scientific cores.